Skin cancers are the most common malignancies in humans and have become a major health problem particularly in the Southwestern region of the United States. Approximately 500,000 basal and squamous cell skin cancers, 27,000 melanomas and 40,000 head and neck cancers were diagnosed in 1988. Although the mortality rate from basal cell and squamous cell skin cancers and oral cancers is relatively low, they are the source of considerable morbidity and health care costs. Melanoma this prognosis continues to be poor, with mortality rates increasing by approximately 3% per year. Because of the extreme importance of these public health problems in Arizona, we have selected as our overall objective to develop effective chemoprevention strategies for both skin and oral cancers. Using specialized research projects, various chemopreventive strategies will be tested in order to design and optimize laboratory-based clinical trials in patients with resected squamous and basal cell skin cancers, actinic keratoses and oral leukoplakia. This integrated approach to patients with established and precancerous skin and oral lesions has led to the structure of the proposed Program Project which features: 1) phase III double- blinded, randomized evaluation of retinol versus placebo in patients with resected basal and squamous cell skin cancers; 2) phase II, randomized trials of beta-carotene in patients with oral leukoplakia and topically administered DFMO in patients with actinic keratoses; 3) a clinical pharmacology project involving the evaluation of beta-carotene in cigarette smoking and non-smoking normal subjects; and 4) an on-going project to evaluate the epidemiology of cutaneous cancers. The scientific projects concerning the evaluation of new chemopreventive agents in a murine photocarcinogenesis model and the mechanisms of melanocyte transformation provide a continuous flow of knowledge to investigators in the clinical projects and cores, who in turn share important information and ideas concerning the epidemiology, cell biology, and pharmacology of skin and oral cancer chemoprevention. The three Cores, Administration, Biometry and Clinical Services (Analytical Chemistry, Dietary and Behavioral Sciences) provide the structure and expertise for the successful execution of the clinical trials and laboratory research studies. A specialized Quality Assurance/Quality Control program further guarantees the success of these projects.